Insulin Resistance in Polycystic Ovarian Syndrome Women: Impact of Regularity and Hyperandrogenemia
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Zainab Hussein Mohammed et al /J. Pharm. Sci. & Res. Vol. 11(2), 2019, 471-476
Insulin Resistance in Polycystic Ovarian Syndrome
Women: Impact of Regularity and
Hyperandrogenemia
Zainab Hussein Mohammed, Maha Abdul Saheb Ridha, Hussein Kadhem Al-Hakeim*
Department of Chemistry, Faculty of Science, University of Kufa, Iraq. *
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and the main cause of infertility due to
anovulation among reproductive-aged women. fetal programming is the beginning of the insulin resistance (IR) and
hyperandrogenism which leads to a chain of health consequences. The disturbances in menstruation and fertility develop
metabolic complications as age advances. An early and precise diagnosis is necessary for a satisfactory management of PCOS,
especially at the extreme ends of the reproductive lifespan. In the present study, IR, hormones and irregularity was studied in
PCOS and compared with the control groups. Sixty PCOS women and thirty apparently healthy women were participated in
the present study. Serum Fasting serum glucose and sugar, prolactine, progesterone, Cortisol, LH, FSH, estradiol, total & Free
testosterone were determined in all women’s. In PCOS women (IR-PCOS) had more obesity comparing with (non IR-PCOS).
HOMA%B and insulin were increased while HOMA%S decreased in IR-PCOS patients in comparing with (non-IR-PCOS).
The IR-PCOS patients had higher LH/FSH, and BMI and lower FSH than Non IR-PCOS. Serum (Insulin, HOMA%B, LH,
LH/FSH) significantly increased in IR-PCOS patients, while serum (FSH, HOMA S%) levels were decreased as compared
with non IR-PCOS. Furthermore, IR-PCOS patients had higher PRG, Cortisol, E2, PRL and lower free Testosterone and total
Testosterone. In Iraqi women with PCOS, IR state is increased as women having irregular menstruation or hyperandrogenism.
Also, PCOS has many changes in hormones and other measured parameters duo to the metabolic bases of the syndrome.
Keywords: Insulin resistance, Polycystic Ovarian Syndrome, Regularity & Hyperandrogenemia.
INTRODUCTION energy, thereby causing the concentration of glucose in the
Polycystic Ovary Syndrome (PCOS) is a hormonal disorder blood to decrease as a result, staying within the normal
that affects between 5-10% women of reproductive age and range even when a large amount of carbohydrates is
remains the most enigmatic reproductive disorders. The consumed. During IR, however, excess glucose is not
most common symptoms of PCOS are insulin resistance sufficiently absorbed by cells even in the presence of
(IR) irregular menstrual cycles obesity, acne, amenorrhea, insulin, thereby causing an increase in the level of blood
hirsutism, and high cholesterol(1). Its hyperandrogenic sugar (7). IR and hyperandrogenism are considered to be a
manifestations include, dyslipidemia, IR, diabetes, cancer, key factors contributing to PCOS, and the exact
infertility and coronary heart diseases (2). PCOS is a mechanisms behind the interactions between IR and
common endocrine disorder affecting females in hyperandrogenism in the female liver is not well
reproductive age. It is a complex disorder whose understood. Hyperandrogenism itself or combined with IR
pathogenesis is not well elucidated despite evidence of contributes to liver damage in women with PCOS (8,9). In
multiple interaction with genetic, behavioral and some PCOS models, elevated testosterone is reported as a
environmental factors that contribute to its occurrence (3). marker of hyperandrogenemia (10). Hyperinsulinemia and
This syndrome is typically characterized by anovulatory hyperandrogenemia are play a prominent roles in PCOS.
cycles and infertility, altered gonadotropin levels, obesity, Insulin signaling in pituitary and the ovaries either directly
and bulky multi follicular ovaries on ultrasound, or indirectly stimulates androgen production (11). Acne and
Hyperandrogenism and IR are hallmark features of its alopecia are not commonly associated with
complex pathophysiology. Hyperandrogenemia is a salient hyperandrogenemia and therefore should not be regarded as
feature of PCOS and a major contributor to cosmetic evidence of hyperandrogenemia (12). Menstrual
anomalies including hirsutism, acne, and male pattern disturbances are common in PCOS, with oligomenorrhoea
alopecia in affected women. Increased androgen levels may and amenorrhoea in different ratios (13, 14). Although the
be intrinsic or aggravated by preexisting IR in women with pathogenesis of PCOS is complex, it is typically associated
PCOS (4). Since IR and resulting compensatory with hyperandrogenism, hyperinsulinaemia and an elevated
hyperinsulinemia are closely related to its pathogenicity ratio of the gonadotropins luteinising hormone (LH) to
and comorbidities, obesity, which is prevalent in a half of follicle-stimulating hormone (FSH) (15). Many factors
PCOS women can be exacerbated (5). IR is a main influence menstrual regularity, including physical activity,
pathophysiologic feature in PCOS women (6) since cells body size, alcohol intake, and smoking, in addition to
fail to respond normally to the insulin. The pancreas pathologic conditions including PCOS (16, 17).
produces insulin when blood glucose starts to be elevated. Approximately 85-90% of women with oligomenorrhea
Under normal conditions of insulin reactivity, this insulin have PCOS, usually defined as cycle length greater than 35
response triggers glucose being taken into body cells, to be days (18). However, the diagnostic criteria for PCOS has
used for energy, and inhibits the body from using fat for evolved over time. Currently, there are three overlapping,
471Zainab Hussein Mohammed et al /J. Pharm. Sci. & Res. Vol. 11(2), 2019, 471-476
but not entirely consistent, clinical definitions of PCOS (19, Exclusion Criteria
20). Menstrual cycle irregularity and length are features The present research excluded the patients with any
included in all three PCOS definitions. Late and irregular obvious major systemic diseases including diabetes
menstrual cycles have been associated with higher mellitus, hereditary diseases, or other endocrine disorders.
androgen and lower sex hormone binding globulin levels
PCOS and this altered hormonal environment may increase Controls
the risk of specific histologic subtypes of ovarian cancer Thirty apparently healthy women were recruited as control
(21). In the present study, IR and irregularity was studied in group. Their age range was 28.73±7.40 year which was
PCOS and compared with the control groups. The comparable to that of patients. None of these subjects were
measured parameters also were correlated with each other pregnant, irregular period, or have other endocrine
in order to estimate the factor affecting parameters levels in disorders.
PCOS group.
Statistical Analysis
MATERIALS AND METHODS Kolmogorov-Smirnov test has been used to examine the
Patients normality distribution of the results. The results of the
Sixty PCOS women patients participated in the study. Their normally distributed variables were expressed as (mean ±
age mean range was 20 to 32 year, All of them were standard deviation). Pooled t-test was used for the
diagnosed with PCOS by gynecology specialist according comparison between the groups. Pearson's correlation
to the European Society of Human Reproduction and coefficients (r) were calculated for the correlationstudy. For
Embryology (ESRHE) consensus conference held in the nonparametric variables, that is not normally
Rotterdam in 2003 (Rotterdam ESHRE/ASRM-Sponsored distributed, the results were expressed as medians, in
PCOS Consensus Workshop Group 2004), American addition to (mean±standard deviation). Mann-Whitney U
Society of Reproductive Medicine (ASRM) and test was used for the comparison and Spearman's
ultrasonography examination in (Center of Fertility in Al- correlation coefficients (ρ rho) were used to estimate the
Sadr Teaching Medical City in Al-Najaf Al-Ashraf correlation between parameters. All statistical analyses
Governorate-Iraq). They were (6-8) hr overnight fasting were performed using SPSS Statistics version 25 program
and on treatment with metformin (Glucophage®). All the (2017), IBM-USA. While the figures constructed using
participated women were having polycysts in their ovaries EXELL program of Microsoft Office 2013.
by ultrasonography examination.BMI calculated from the
following equation: BMI=Weight (Kg)/Height (m2) (22), RESULTS
When BMI was larger than 30 Kg/m2, the person was The comparison between PCOS patients and controls in the
defined obese. All hormones were calculated by using Elisa measured parameters is presented in Table 1. There is a
Kit (The enzyme-linked immunosorbent assay). The significant increase in BMI, WHR, insulin, HOMA2IR,
estimate of serum Glucose, Total Protein provided by HOMA%B, LH, E2, Prolactin, T.Testo and F.testo in
CYPRESS DIAGNOSTICS. The computer based HOMA2 PCOS patients group in comparing with the control group.
calculator (available at www.dtu.ox.ac.uk/homa) (Figure 1) The comparisons between regular and irregular PCOS
uses fasting insulin and glucose concentrations to calculate women in different parameters are presented in Table 2.
the index of IR, HOMA2IR, and the index of β cell Thirty-eight out of sixty PCOS women (63.4%) were
function (HOMA-%B). In ideal normal-weight individual irregular and 22 patients were regular (36.6%).
ageZainab Hussein Mohammed et al /J. Pharm. Sci. & Res. Vol. 11(2), 2019, 471-476
Table 2: Comparison between PCOS patients with regular and irregular Cycle.
PCOS with
Parameter PCOS with Regular Cycle n=22 Significance
Irregular Cycle n=38
Age(year) 26.13±6.67 29.45±8.765 N.S
BMI(kg/m2) 28.67±7.60 26.11±8.03 N.S
WHR 0.7803±0.20 0.8266±0.04 N.S
FBS 83.75±13.78 87.70±42.63 N.S
Insulin(µIU/ml) 16.56 7.21 0.006
I/G 3.65±2.71 3.69±3.82 N.S
HOMA2IR 2.68 1.64 0.031
HOMA%B 94.65 83.59 0.027
HOMA%S 88.52 91.22 N.S
FSH (mIU/ml) 12.62±5.23 10.99±4.76 N.S
LH(mIU/ml) 12.48 11.26 N.S
LH/FSH 1.32±1.03 1.18±0.70 N.S
Cortisol(µg/dI) 13.25 7.85 0.008
E2(pg/ml) 46.08±19.74 42.68±14.39 N.S
PRL.(ng/ml) 17.33±8.38 19.38±7.36 N.S
Prog.(ng/ml) 0.93±0.03 0.94±0.04 N.S
F.Testo. (pg/ml) 4.38 2.14 0.024
T.Testo. (ng/ml) 0.72±0.15 0.61±0.11 0.043
Table 3: Comparison between IR patients (HOMA2IR≥3) and non-IR patients.
IR-PCOS Non-IR-PCOS
Parameters Significance
(HOMA2IR≥3) (n=15) (HOMA2IRZainab Hussein Mohammed et al /J. Pharm. Sci. & Res. Vol. 11(2), 2019, 471-476
(29.79±6.29 vs. 24.73±8.85 kg/m2, p=0.021); F.Teso (2.85 correlations were found between BMI, free testosterone and
vs. 5.12 pg/ml, p=0.08) than the corresponding patients HOMA-IR (37). Farthermore, F.Testo. level is more
without acne (p=0.021). The following IR parameters also sensitive than the measurement of total T.testo. for
showed an increase in patients with acne in comparing with establishing the existence of androgen excess and should be
patients without acne (Insulin=17.3 vs. 11.54 µlU/ml, ideally determined through equilibrium dialysis techniques.
p=0.014; I/G= 3.12 vs. 4.68, p=0.23; HOMA%B= 91.86 vs. Value of measuring levels of androgens other than T in
88.42, p=0.021). patients with PCOS is relatively low (38). Daghestani et al
(2018) (39) showed in their results that patients in the
DISCUSSION PCOS group exhibited increases in testosterone (202.3%),
The results in Table 1 showed the typical results fasting glucose (9.2%), fasting insulin (49.4%), LH/FSH
of the PCOS as a syndrome related to IR, and hormonal ratio (205.3%), and decreases in progesterone (-7.4%).
disturbances (24-25). In the present research, only fifteen While Zhang et al 2018 (40) found The levels of LH,
patients out of 60 (25%) are insulin resistant (IR-PCOS) LH/FSH, T.testo, fasting insulin and homeostasis model
and 45 out of 60 patients (75%) are non-IR (non IR-PCOS) assessment of IR (HOMA2IR) index in PCOS group were
and they had significantly higher BMI (obese) than (nonIR- higher than those in normal control group. A significant
PCOS) This result has been recorded with Miriam et al (26) difference was found in basal LH, fasting glucose, insulin,
found ratio of IR diagnoses was higher in obese women HOMA-IR, F.Testo levels, WHR ratios between the PCOS
than in normal BMI women. they observed a significant and non-PCOS patients in the lean and overweight groups
association between IR and BMI. Even though obesity is (pZainab Hussein Mohammed et al /J. Pharm. Sci. & Res. Vol. 11(2), 2019, 471-476
In our study we find that PCOS patients with and syndrome (PCOS): the Amsterdam ESHRE/ ASRM-Sponsored 3rd
PCOS Consensus Workshop Group. Fertil Steril. 2012; 97(1):28-
without facial hair groups revealed a significant difference 38.e25.
in the following parameters (Cortisol (11.65 vs. 9.41µg/dI), 13. Balen AH, Conway GS, Kaltsas G et al. Polycystic ovary syndrome:
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